AVROBIO Gene Therapy Education

AVROBIO Gene Therapy Reference

02 Understanding Cell Therapy

Section 3

Overview of Hematopoietic Stem Cells (HSCs)

Learning Goal

To understand the function of hematopoietic stem cells

Hematopoiesis is the process by which blood cells are continuously replaced over the entire lifetime of an individual.1 Hematopoietic stem cells (HSCs) and their progenitor cells, which are early descendants of HSCs that can form one or more cell type, but cannot divide and reproduce indefinitely, are called HSPCs. HSPCs are multipotent, blood-forming stem cells that can self-renew to produce all the types of blood cells: red blood cells, white blood cells including macrophages, and platelets, among others (see Figure). The greatest number of HSPCs can be found in adult bone marrow, though they can also be found at low levels in the peripheral blood cells.2,3

Hematopoietic Stem Cells1,4

Human HSPCs are also known as CD34+ cells because they uniquely express a protein on their surface called cluster of differentiation (CD) 34. They are selected for use in hematopoietic stem cell transplants (HSCTs) because of their ability to home to the bone marrow, enabling the continued production of blood cells throughout the recipient’s lifetime.5-8 Clinical studies demonstrate that some of the CD34+ cells form specialized daughter cells called monocytes which can enter the brain, where they become microglial cells that are essential to the function of the central nervous system (CNS, consisting of the brain and spinal cord).9,10  

Additional Interesting Fact

The body makes about 300 billion new blood cells daily, including red blood cells, platelets, and neutrophils (a type of white blood cell).1

Key Learnings

Hematopoietic stem cells and their progenitor cells (HSPCs) are multipotent blood-forming stem cells that are mainly found in the bone marrow.

HSPCs can produce all types of blood cells, including red blood cells, white blood cells, and platelets, as well as microglial cells throughout the CNS.

HSPCs, also known as CD34+ cells, are used in hematopoietic stem cell transplants (HSCTs) because of their ability to home to the bone marrow so that blood cells can be made throughout the recipient’s lifetime.

Continue learning about cell therapy in the next section

Section 4

What is Hematopoietic Stem Cell Therapy?

To learn about the different ways hematopoietic stem and progenitor cells can be used to treat disease.

Next Section ››

References

  1. Aiuti A, Scala S, Chabannon C. Biological Properties of HSC: Scientific Basis for HSCT. In: Carreras E, Dufour C, Mohty M, et al., editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies [Internet]. 7th edition. Springer; 2019. https://www.ncbi.nlm.nih.gov/books/NBK553952/. doi: 10.1007/978-3-030-02278-5_7. Accessed December 22, 2021.
  2. Gene and cell therapy FAQ’s. American Society of Gene & Cell Therapy; 2021. https://www.asgct.org/education/more-resources/gene-and-cell-therapy-faqs. Accessed December 22, 2021.
  3. Glossary. American Society of Gene & Cell Therapy; 2021. https://www.asgct.org/education/more-resources/glossary. Accessed December 22, 2021.
  4. Wei Q, Frenette PS. Niches for hematopoietic stem cells and their progeny. Immunity. 2018;48(4):632-648. [PubMed]
  5. CD34. The Free Dictionary. Available at: https://medical-dictionary.thefreedictionary.com/CD34. Accessed December 22, 2021.
  6. Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A. Concise review: evidence for CD34 as a common marker for diverse progenitors. Stem Cells. 2014;32:1380-1389. [PubMed]
  7. What are progenitor cells? Boston Children’s Hospital; 2021. http://stemcell.childrenshospital.org/about-stem-cells/adult-somatic-stem-cells-101/what-are-progenitor-cells/. Accessed December 22, 2021.
  8. Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood. 2005;106(6):1901-1910. [PubMed]
  9. Wolf NI, Breur M, Plug P, et al. Metachromatic leukodystrophy and transplantation: remyelination, no cross-correction. Ann Clin Transl Neurol. 2020;7(2):169-180. [PubMed]
  10. Peterson CW, Adair JE, Wohlfahrt ME, et al. Autologous, gene-modified hematopoietic stem and progenitor cells repopulate the central nervous system with distinct clonal variants. Stem Cell Reports. 2019;13(1):91-104. [PubMed]